DNA methylation profile discriminates sporadic giant cell granulomas of the jaws and cherubism from their giant cell-rich histological mimics.

Sporadic giant cell granulomas (GCGs) of the jaws and cherubism-associated giant cell lesions share histopathological features and microscopic diagnosis alone can be challenging. Additionally, GCG can morphologically closely resemble other giant cell-rich lesions, including non-ossifying fibroma (NOF), aneurysmal bone cyst (ABC), giant cell tumour of bone (GCTB), and chondroblastoma. The epigenetic basis of these giant cell-rich tumours is unclear and DNA methylation profiling has been shown to be clinically useful for the diagnosis of other tumour types. Therefore, we aimed to assess the DNA methylation profile of central and peripheral sporadic GCG and cherubism to test whether DNA methylation patterns can help to distinguish them. Additionally, we compared the DNA methylation profile of these lesions with those of other giant cell-rich mimics to investigate if the microscopic similarities extend to the epigenetic level. DNA methylation analysis was performed for central (n = 10) and peripheral (n = 10) GCG, cherubism (n = 6), NOF (n = 10), ABC (n = 16), GCTB (n = 9), and chondroblastoma (n = 10) using the Infinium Human Methylation EPIC Chip. Central and peripheral sporadic GCG and cherubism share a related DNA methylation pattern, with those of peripheral GCG and cherubism appearing slightly distinct, while central GCG shows overlap with both of the former. NOF, ABC, GCTB, and chondroblastoma, on the other hand, have distinct methylation patterns. The global and enhancer-associated CpG DNA methylation values showed a similar distribution pattern among central and peripheral GCG and cherubism, with cherubism showing the lowest and peripheral GCG having the highest median values. By contrast, promoter regions showed a different methylation distribution pattern, with cherubism showing the highest median values. In conclusion, DNA methylation profiling is currently not capable of clearly distinguishing sporadic and cherubism-associated giant cell lesions. Conversely, it could discriminate sporadic GCG of the jaws from their giant cell-rich mimics (NOF, ABC, GCTB, and chondroblastoma).

Surgical excision of peripheral giant cell granuloma of the maxilla: a case report.

Peripheral giant cell granuloma (PGCG) is described as an elevated lesion that is located mostly on the gingival mucosa and alveolar crest, consecutive to irritative factors and trauma. It predominantly occurs more in the mandible than the maxilla, and it is usually seen in the 4th to the 6th decades. The clinical appearance of this lesion is red-bluish in color, presenting a similar tissue to the one observed in the liver, usually measuring less than 2 cm. The treatment of the PGCG is the surgical excision. The recurrence of this lesion is rarely described in the literature. The present case highlights the importance of considering the traumatic extractions as one of the main uncommon etiologic factors, leading to the development of peripheral giant cell granuloma. It precisely describes the diagnosis, the treatment of a peripheral giant cell granuloma located in maxillary canine-premolar region, occurred consecutively after ancient traumatic extractions of the 13 and 14 since 1 year. This paper also reports a maxillary location of giant cell granuloma, while the literature reports more commonly the mandibular location. This lesion was excised surgically, and healed uneventually, and in which the follow-up didn´t show any sign of recurrence.

Excision of a Benign Peripheral Giant Cell Granuloma in the Oral Mucosa of the Anterior Mandibular Teeth with a 975-nm Diode Laser: A Case Report of a 39-Year-Old Woman.

BACKGROUND Peripheral giant cell granuloma, or epulis, is a common and benign oral lesion that can grow rapidly. Diode lasers are increasingly used to excise soft-tissue lesions because the technique preserves tissue for histopathology while controlling bleeding. Here, we report the excision of a 2-cm benign peripheral giant cell granuloma of the oral mucosa by 975-nm infrared diode laser, with rapid wound healing and good tissue preservation for histological analysis. CASE REPORT A 39-year-old woman presented with a large red-purple lesion in the oral mucosa of the lower jaw, near teeth 41 and 32. According to the patient, despite the absence of pain, the lesion caused difficulty while eating, speaking, and maintaining oral hygiene. The periodontal assessment included the following parameters: clinical attachment level, gingival recession, pocket probing depth, Loe-Silness gingival index, and tooth mobility index. The lesion was excised under local anesthesia using a 975-nm diode laser, and histopathology reports confirmed the diagnosis of peripheral giant cell granuloma. Six weeks after removal of the peripheral giant cell granuloma, all periodontal parameters were improved except for clinical attachment level and gingival recession. CONCLUSIONS Excision by 975-nm infrared diode laser can maintain tissue integrity for histopathology while allowing complete excision and control of bleeding. Soft lasers can provide advantages such as reduced bleeding, less operative and postoperative pain, decreased mechanical trauma, increased patient acceptability, and rapid wound healing without sutures, and they can be used to successfully remove peripheral giant cell granulomas.

Response of Central Giant Cell Granuloma of the Jaw to Imatinib.

Central giant cell granuloma of the jaw (CGCJ) can be locally aggressive and result in facial and dental deformity. A child with CGCJ was treated surgically and with denosumab with a response but life-threatening toxicity. Imatinib, a tyrosine kinase inhibitor, was prescribed based on clinical similarities between CGCJ and cherubism, for which Imatinib has been effective. Within 2 months, a computed tomographic scan showed significant ossification, which increased over the following 8 months. This case suggests that tyrosine kinase inhibitors may be an effective option, and one with limited toxicity, for CGCJ.

Giant cell epulis.

Giant cell epulis (peripheral giant cell granuloma) typically appears as a reactive benign lesion in the oral cavity in areas following local irritation or chronic trauma. Here we describe the case of a 45-year-old male patient who presented with the chief complaint of a large gingival mass in the anterolateral maxilla. There had been progressive growth within the past few months, with increased painless discomfort during mastication. The patient also reported bleeding during interdental cleaning. A full physical work-up led to the suspicion of giant cell epulis alongside other differentials including mucosal hemangioma and squamous cell carcinoma, with unremarkable laboratory values. Imaging including computed tomography showed signs of previous insertion of metal implants on either side of the lesion alongside mucosal hyperplasia. A confirmatory biopsy was taken and showed multiple giant cells on a reactive bed of stroma, in line with the diagnosis of giant cell epulis. Oral inflammatory conditions such as giant cell epulis have greater chances of local recurrence and, therefore, careful investigation with timely and accurate diagnosis is imperative for appropriate early treatment. Complete surgical excision should then be employed to prevent relapses, as incomplete removal can lead to further recurrence. Identification and eradication of potential sources of irritation should also be considered when treating the patient, to avoid further recurrence.

Significant association between FGFR1 mutation frequency and age in central giant cell granuloma.

Central giant cell granulomas (CGCG) are rare intraosseous osteolytic lesions of uncertain aetiology. Despite the benign nature of this neoplasia, the lesions can rapidly grow and become large, painful, invasive, and destructive. The identification of molecular drivers could help in the selection of targeted therapies for specific cases. TRPV4, KRAS and FGFR1 mutations have been associated with these lesions but no correlation between the mutations and patient features was observed so far. In this study, we analysed 17 CGCG cases of an Italian cohort and identified an interesting and significant (p=0.0021) correlation between FGFR1 mutations and age. In detail, FGFR1 mutations were observed frequently and exclusively in CGCG from young (<18 years old) patients (4/5 lesions, 80%). Furthermore, the combination between ours and previously published data confirmed a significant difference in the frequency of FGFR1 mutations in CGCG from patients younger than 18 years at the time of diagnosis (9/23 lesions, 39%) when compared to older patients (1/31 lesions, 0.03%; p=0.0011), thus corroborating our observation in a cohort of 54 patients. FGFR1 variants in young CGCG patients could favour fast lesion growth, implying that they seek medical attention earlier. Our observation might help prioritise candidates for FGFR1 testing, thus opening treatment options with FGFR inhibitors.

A Unique Case of Aggressive Central Giant Cell Granuloma in a 10-Year-Old Boy With 16p13.11 Microdeletion Syndrome.

Central giant cell granuloma (CGCG) is a rare disease characterized by sporadic, benign, intraosseous mandibular lesions of unknown etiology. Histologically, these lesions are indistinguishable from brown tumors of hyperparathyroidism and cherubism, and occasionally have been associated with different syndromes raising a question for genetic etiology. The CGCG has varied presentation ranging from nonaggressive and indolent to aggressive, destructive, and recurrent, often posing diagnostic and therapeutic challenges. Herein, we present the first case of a 10-year-old boy with CGCG and 16p13.11 microdeletion syndrome, highlight the diagnostic challenges inherent to this heterogeneous disorder, and discuss the genetics and treatment approaches of these complex lesions.

Diagnóstico e tratamento de granuloma periférico de células gigantes em mandíbula - relato de caso / Diagnosis and treatment of peripheral granuloma of giant cell in the jaw - case report

O granuloma periférico de células gigantes (GPCG) é uma lesão hiperplásica benigna causada por trauma local ou trauma crônico. Origina-se do ligamento periodontal ou mucoperiósteo. O objetivo deste trabalho é apresentar um caso de GPCG em mandíbula tratada com sucesso através de excisão cirúrgica, curetagem e ostectomia periférica.

Peripheral giant cell granuloma (PGCG) is a benign hyperplastic lesion caused by local trauma or chronic trauma. It originates from the periodontal ligament or mucoperiosteum. The objective of this work is to present a case of PGCG in the mandible successfully treated through surgical excision, curettage and peripheral ostectomy.

A rare case of a giant cell tumour caused by vitamin D deficiency.

Reparative giant cell granulomas are benign masses of multi-etiological nature, which account for 1%-7% of all benign lesions of the jaws. The objective of this case report is to present the relationship between isolated vitamin D deficiency and the development of reparative giant cell granuloma.Herein, we present the case of a 70-year-old female patient with a painless mass of increased mobility in the mandibular region, and pain in the involved teeth. After histological confirmation and laboratory screening, а reparative giant cell granuloma caused by serious deficiency of vitamin D3 - (25-OH)D was diagnosed. The treatment protocol included surgical removal of the lesion and vitamin D replacement therapy.In rare cases, this type of lesion can be a primary manifestation of vitamin D deficiency; therefore, it is extremely important to be aware of this pathology.

Central giant cell granuloma of the head & neck: A case report and systematic review.

PURPOSE: The purpose of this paper is to describe a recent case of central giant cell granuloma (CGCG) that rapidly progressed post corticosteroid treatment while also providing a review of the existing literature on CGCG of the head and neck (HNCGCG), with particular emphasis on extra-mandibular and maxillary cases. MATERIALS AND METHODS: The investigators designed and implemented a 32-year review of literature, using the online databases: PubMed, Google Scholar, Medline, and Proquest. The total number of cases analyzed was 55 (42 case reports; 3 case series; 8 comparative studies; 1 retrospective cohort). CASE PRESENTATION: We present a case of a CGCG in a 10-year old male. The lesion originated in the right anterior mandibular body and progressed after corticosteroid treatment. Diagnosis was made using a combination of imaging and histology. A timely debulking procedure of the hemi-mandible was performed and there was no recurrence of the lesion at follow up. RESULTS: The average age at the time of diagnosis of CGCG was 27.5 years. HNCGCG was most commonly detected in the jaw (43.1%), but was also found in the temporal bone (33.3%). The most frequently employed treatment modality was complete surgical excision (76.9%). 93.2% of patients were alive with no evidence of disease at follow-up, while 6.8% of patients exhibited recurrence at follow-up. The median follow up was 13 months. CONCLUSION: It is important for clinicians to recognize that CGCGs are capable of manifesting outside of the jaw. CGCG should be considered in the differential diagnosis of non-odontogenic radiolucent lesions, especially in young patients. CGCGs also need to be distinguished from brown tumor of hyperparathyroidism (BTH) and giant cell tumors, which are histologically similar.

HAS Carnoy's solution a role in the management of recurrent peripheral giant cell granuloma?

OBJECTIVE: this study aimed to evaluate the efficacy of local application of Carnoy's solution following the surgical excision of recurrent PGCG. PATIENTS AND METHODS: 40 patients who sought treatment for recurrent PGCG were included in this study. According to the type of treatment the patients were classified randomly into two equal groups. The lesions in all patients were excised down to the alveolar bone followed by aggressive curettage. Then only in group II, Carnoy's solution was applied for 5 min. Clinical follow-up was done for 1 year to evaluate the tissue healing. RESULTS: patients were 23 females and 17 males, with an average of 35.9years. Recurrent PGCGs occurred most commonly in fifth decade of life (25 %). Maxilla (57.5 %) was involved more than the mandible. The lesions were found posteriorly in 27cases and anteriorly in 13cases. The average size of the lesions was 2.9 cm. Histologically, foci of calcifications occurred in 12cases. Recurrence occurred in 5 cases: 4 in group I and 1 in group II. Bone healing was appropriate in all patients without sequestration. CONCLUSION: the use of Carnoy's solution following surgical removal of recurrent PGCG decreases their recurrence rates. The technique is safe, and conservative with low tissue morbidity.

Pediatric Aggressive Benign Mandibular Tumors: Clinical Features and Management.

INTRODUCTION: Aggressive benign mandibular tumors are uncommon in the pediatric population, and there is few publishing in the literature specifically dealing with them. Aggressive tumors can be defined based on known biologic behavior and/or histologic type and/or clinical characteristics. AIM OF THE STUDY: To review the clinical features and management of lower jaw pediatric aggressive benign tumor. PATIENTS AND METHODS: Medical records review of pediatric patients presented with aggressive benign mandibular tumors to the Maxillofacial and Plastic Surgery Department, University of Alexandria, Egypt between 2011 and 2019. RESULTS: Fifty-eight patients were included in this study, aged between 2 and 16 years (average = 11.8). Ameloblastoma was the commonest pathological diagnosis (n = 18) followed by central giant cell granuloma (n = 11) and juvenile ossifying fibroma (n = 10). Patients with central giant cell granuloma were treated by en-block resection (n = 4) or curettage after interferon alfa injection (n = 7). All other benign tumors were treated by en-block resection. The length of follow-up ranged from 1 to 8 years. Successful reconstruction was accomplished in 45 patients (88.2%). CONCLUSIONS: Aggressive lesion should be treated in an aggressive manner and immediate reconstruction is advocated. However, pharmacotherapy combined with enucleation is a more conservative approach for management of aggressive central giant cell tumors.

Giant Cell-Rich Tumors of Bone.

The term giant cell-rich tumors of bone refers to a shared morphologic pattern in a group of different osseous lesions, that is, the abundance of osteoclastlike giant cells. Fitting with a broad spectrum of clinical presentations and biological behavior, the recent detection of characteristic molecular alterations in giant cell tumor of bone (H3-3), nonossifying fibroma (KRAS, FGFR1), giant cell granuloma of the jaws (KRAS, FGFR1, TRPV4), and aneurysmal bone cyst (USP6) have contributed significantly to the biological understanding of these morphologically related but clinically distinct lesions and their systematic classification, highlighting differences and pathogenic relationships.

Giant cell reparative granuloma of the phalanx in a violinist.

Giant cell reparative granuloma (GCRG) is a rare, pseudotumoural intraosseous lesion, considered a reactive injury after repeated trauma. Reactive lesions and benign bone tumours may show aggressive clinical and radiographic findings. Differential diagnosis must be performed in order to offer suitable treatment to the patient. Excisional biopsy and curettage of the lesion are the preferred methods of treatment. We present the first case of a GCRG of the distal phalanx of the left little finger in a professional violinist.

Can Methotrexate be a successful treatment for unresponsive generalized annular elastolytic giant cell granuloma? Case report and review of the literature.

Annular elastolytic giant cell granuloma (AEGCG) is a rare granulomatous skin disorder, characterized by erythematous plaques with elevated borders and hypopigmented center, occurring mainly on sun exposed-skin. Histologically it presents with elastophagocytosis and elastolysis. There is no established first line treatment for AEGCG, especially for the generalized form. In a small number of cases, antimalarial drugs and tranilast, associated to topical or oral steroids, have been proposed to treat generalized AEGCG with partial benefits. We herein present the case of a patient with AEGCG aged 74 years, who was unresponsive to classical therapies, and then successfully treated with methotrexate.

Granuloma piógeno oral recurrente con pérdida ósea alveolar y movilidad dentaria: Reporte de un caso inusual / Granuloma piogênico oral recorrente com perda óssea alveolar e mobilidade dental: Relato de um caso incomum / Recurrent oral pyogenic granuloma with alveolar bone loss and tooth mobility: report of an unusual case

Resumen El granuloma piógeno oral es una lesión benigna multifactorial, caracterizada por presentarse como un agrandamiento gingival muy vascularizado. Se puede localizar en cualquier área de la cavidad oral, con más frecuencia en la encía marginal vestibular. Se presenta con mayor incidencia en mujeres adultas y en niños varones. No suele comprometer tejido óseo ni dientes y su tratamiento más seguro es la exéresis quirúrgica, siendo el riesgo de recurrencia alto. El objetivo del presente estudio es reportar el caso de una paciente de 9 años de edad, que fue sometida a la exéresis de un granuloma piogénico oral en el hueso maxilar y al año siguiente presentó una recurrencia de la lesión con pérdida ósea alveolar y movilidad de un diente adyacente. Se le realizó una biopsia y un curetaje minucioso, confirmándose el diagnostico de granuloma piogénico oral.

Resumo O granuloma piogênico oral é uma lesão multifatorial benigna, caracterizada por apresentarse como um aumento gengival altamente vascularizado. Pode estar localizado em qualquer área da cavidade oral, mais frequentemente na gengiva marginal vestibular. Ocorre com maior incidência em mulheres adultas e em crianças do sexo masculino. Geralmente não compromete o tecido ósseo ou os dentes e seu tratamento mais seguro é a escisão cirúrgica, sendo alto o risco de recorrência. O objetivo do presente estudo é relatar o caso de uma paciente de 9 anos de idade, submetida a escisão de granuloma piogênico oral no maxilar e no ano seguinte apresentou uma recorrência da lesão com perda óssea alveolar e a mobilidade de umo de seus dentes adjacentes. Uma biópsia e uma curetagem completa foram realizadas, confirmando o diagnóstico de granuloma piogênico oral.

Abstract Oral pyogenic granuloma is a benign multifactorial lesion that appears as a highly vascular gingival enlargement. It can be located anywhere in the oral cavity, most often in the vestibular marginal gingiva. It occurs most frequently in adult women and male children. It does not usually compromise bone tissue or teeth; its safest treatment is surgical excision, with a high recurrence risk. This study aims to report the case of a 9-year-old female patient who underwent oral pyogenic granuloma excision in the maxilla. The following year, she presented a possible lesion recurrence with alveolar bone loss and the mobility of an adjacent tooth. A biopsy and thorough curettage were performed, confirming the diagnosis of oral pyogenic granuloma.

Intramandibular plexiform schwannoma presenting as a nonspecific benign lesion: How specific can we be? A case report with a review of the literature.

Schwannoma, a benign nerve sheath tumor, is quite rare and more so in jawbones. We report a rare case of a plexiform variant of mandibular schwannoma in a 12-year-old female with a swelling in the left mandible. Clinical features were suggestive of dentigerous cyst as a result of missing premolars and canine. Occlusal and panoramic radiography revealed an osteolytic lesion with scalloping margins, bicortical plate expansion, and agenesis of several teeth. Odontogenic keratocyst, central giant cell granuloma, odontogenic myxoma, and ameloblastic fibroma were given as radiological differential diagnoses. Histopathological examination revealed features of plexiform schwannoma which was given as the final diagnosis. The lesion was treated with surgical excision. Although odontogenic cysts/tumors are often thought of in differential diagnosis whenever well-defined radiolucencies in the jaw are encountered, it is prudent to include schwannoma. This exceptional case adds light to the fact that schwannoma should not be overlooked though it is a rare possibility and must be included in differential diagnosis of odontogenic cysts/tumors.

An unusually large peripheral giant cell granuloma: a case report / Granuloma periférico de células gigantes inusualmente grande: reporte de un caso

Peripheral giant cell granuloma (PGCG) is a benign reactive lesion of the oral cavity. Although PGCG is classified as a tumor-like lesion, it does not represent a true neoplasm, however it is often associated with a response of local irritation and trauma. Clinically, it appears as an exophytic growth with either sessile or pedunculated base, it can be located in gingiva or edentulous alveolar mucosa and usually does not exceed two cm in diameter. The following report describes the case of a 64-year-old female diagnosed with a PGCG of a particularly large size and rapidly evolving, located in the upper jaw area. The lesion was completely excised, and the diagnosis was confirmed by histopathology, there is no apparent recurrence in the area after 12 months of follow-up. A few cases of PGCG greater than 5 cm in diameter have been reported. Furthermore, exceptional cases might present an abnormal rapid growth as well. An opportune diagnosis based on clinical examination, radiographic and histopathological study are fundamental for a prompt and efficient treatment

El granuloma periférico de células gigantes (GPCG) es una lesión reactiva benigna de la cavidad oral en respuesta a una irritación local o a un traumatismo crónico. Si bien es una lesión de aspecto tumoral, no constituye una verdadera neoplasia. Se manifiesta como un crecimiento exofítico de base sésil o pediculada, localizado en encía o procesos alveolares edéntulos y no suele sobrepasar los 2 cm de diámetro. El presente reporte describe el caso de un GPCG de tamaño anormalmente grande y rápida evolución localizado en la zona del maxilar superior en un paciente femenino de 64 años. La biopsia escisional de la lesión confirmó el diagnóstico de GPCG y a 12 meses de seguimiento no se ha presentado recidiva. Se han reportado algunos casos de GPCG de más de 5 cm de diámetro. Además, casos excepcionales también pueden presentar un crecimiento rápido anormal. Un diagnóstico oportuno basado en el examen clínico, radiográfico e histopatológico es fundamental para un tratamiento rápido y eficaz